A number of radioimmunoassays have been adapted for use in our laboratory, enabling rapid determinations of ACTH, cortisol, prolactin, beta-endorphin, and growth hormone levels in plasma and cerebrospinal fluid of monkeys and man. With these assays, we have initiated a series of studies designed to characterize the diurnal rhythms and regulatory mechanisms of a number of hormones which reflect hypothalamic-pituitary activity in rhesus monkeys and man. A specific circadian cortisol rhythm has been characterized in the CSF of monkeys similar to that previously reported for man. Biologically active opioid peptides in CSF of rhesus monkeys and human plasma have been demonstrated to have a similar diurnal pattern to that of ACTH. A low dose-response relationship has been determined by dexamethasone suppression of plasma cortisol levels in monkeys. At levels of dexamethasone sufficient to suppress plasma cortisol levels, beta-endorphin immunoreactivity in plasma remains unchanged, suggesting some previously unappreciated differences in the regulation of the secretion of these two hormones. In addition, we have initiated studies of the neuroendocrine changes accompanying specific pharmacologic challenges, e.g. neuroendocrine changes accompanying development of the physostigmine behavioral syndrome in man.